The binding of a regulatory protein to DNA brings together two complementary surfaces, each of which interacts with water and ions in solution. When the two macromolecules bind, some of these interactions with the milieu are lost, and new interactions with the complementary surface are formed. This makes the extent of binding very sensitive to solution conditions. In addition, DNA-mediated protein-protein interactions (e.g. DNA looping), are an important part of the biological activity of most transcriptional regulators. Varying the solution oncotic pressure (by adding high concentrations of an excluded solute) allows one to determine the effect of surface hydration of both protein and DNA on complex formation. This allows one to determine the total number of water molecules released in the binding reaction, which should be related to the amount of surf ace area of both protein and DNA occluded in the complex. Such insight into the hydration of both surfaces before and after complexation is important for understanding the sources of stability and specificity of a protein-DNA complex.